HIV-infection and it treatments are associated with a cluster of metabolic and anthropomorphic complications that increase cardiovascular disease (CVD) risk. CVD pathogenesis in HIV is multifactorial, so safe and effective treatments that protect against or prevent CVD progression are essential for reducing CV morbidity and mortality in people living with HIV. Over the past 4yrs, we have found that pioglitazone improves insulin sensitivity, but that exercise training enhances the peripheral insulin sensitizing actions of pioglitazone in HIV+ people with insulin resistance (IR) and central adiposity. Recent evidence indicates that pioglitazone and peroxisome proliferator-activated receptor agonists (PPARs) possess anti-inflammatory, anti-atherogenic, and positive ionotropic properties in T2DM with CVD risk profiles (not incl.heart failure). We now propose that pioglitazone + exercise training will reduce vascular inflammation, improve endothelial function, reduce atherogenesis, reduce myocardial lipid content and improve left ventricular function in people living with HIV+IR and CVD risk profiles. We hypothesize that pioglitazone + exercise training provides greater anti- inflammatory, anti-atherogenic, and pro-ionotropic actions than either pioglitazone or exercise training alone. We propose to use novel radiotracer-PET/CT imaging measures of vascular inflammation and macrophage infiltration, state-of-the-art non-invasive imaging techniques to quantify vascular and left ventricular function and myocardial lipid content, and a sensitive mass spectrometry technique to quantify a serum marker of lipid peroxidation (8-iso-PGF2[unreadable]) in people living with HIV+IR+CVD risk profiles before and after 6-months of pioglitazone, exercise training or the combination. We anticipate that this project will provide direct evidence that pioglitazone + exercise training reduce CVD risk in HIV+IR by reducing vascular inflammation and early proatherogenic events, and by enhancing left ventricular contractile function.